Ann Surg Oncol (2018) 25:2105–2110

https://doi.org/10.1245/s10434-018-6513-7

EDITORIAL – MELANOMAS

Melanoma Staging: American Joint Committee on Cancer

(AJCC) 8th Edition and Beyond
Jeffrey E. Gershenwald, MD1,2 and Richard A. Scolyer, MD3,4,5

1
Departments of Surgical Oncology and Cancer Biology, Unit 1484, The University of Texas MD Anderson Cancer
Center, Houston, TX; 2Melanoma and Skin Center, The University of Texas MD Anderson Cancer Center, Houston, TX;
3
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; 4Department of Tissue Pathology and
Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; 5Sydney Medical School, The
University of Sydney, Sydney, NSW, Australia

Melanoma staging is a critical tool for communication stage IV patients in their initial data analyses of the
between physicians and their patients and also assists IMDDP. Therefore, patients eligible to be included in the
clinical decision-making and prognostic assessment. It is IMDDP were those with stages I–III cutaneous melanoma
used for clinical trial design, eligibility, stratification, and diagnosed since 1998. This approach allowed us to exclude
analysis. Importantly, it also represents the foundation for patients diagnosed during the early and mid-1990s, a per-
reporting in institutional, state, national, and international iod of rapid evolution in surgical, pathological, and nuclear
data registries, which, in turn, facilitate understanding of medicine strategies employed to identify, remove, and
the broader melanoma landscape. accurately assess the sentinel lymph node (SLN) in patients
The 7th edition AJCC melanoma staging system was with cutaneous melanoma who underwent lymphatic
introduced in 2009 and implemented in 2010. Since that mapping and SLN biopsy. In contrast, the database used for
time, there has been a tremendous improvement in our the 7th edition had no restriction on the date of diagnosis
understanding of the molecular and immune biology of and included patients diagnosed as long ago as the 1960s.8
melanoma, which has led to the unprecedented introduction In addition, for inclusion in the 8th edition analyses,
and widespread use of a number of effective systemic patients were required to have undergone SLN biopsy if
therapies for patients with advanced disease and in the their primary was T2 or thicker, and if T1 and a SLN
adjuvant setting.1–6 biopsy had been performed, SLN status was incorporated
To facilitate an evidence-based approach and to inform for data analysis and staging purposes.
revisions for the 8th edition of the AJCC melanoma staging The TNM- or anatomic-based staging system is effec-
system, we created a contemporary international melanoma tively constrained by the limited type and number of
database: the International Melanoma Database and Dis- factors that can be included. However, both anatomic and
covery Platform (IMDDP).7 Given the recent advances in nonanatomic factors can have significant prognostic
the clinical management of patients with advanced and importance. As such, the overall 8th edition AJCC strategy
unresectable disease, rapidly evolving treatment options for embraced inclusion of standard anatomic ‘‘TNM’’ prog-
such patients and varying approval for use of these new nostic factors and also considered nonanatomic factors that
agents in different parts of the world, the AJCC melanoma could help further improve staging and prognostic
expert panel considered that it was inappropriate to include assessment.9

T CATEGORY AND STAGES I/II STAGE GROUPS

Ó Society of Surgical Oncology 2018
In the 7th edition, T-category criteria included tumor
First Received: 21 March 2018;
Published Online: 30 May 2018 thickness (measured to the nearest 0.01 mm) and presence
or absence of ulceration across all subcategories; mitoses
J. E. Gershenwald, MD
e-mail: [email protected] as a dichotomous variable (\ 1 vs. C 1 mitosis/mm2) also
2106 J. E. Gershenwald, R. A. Scolyer

was included as a T1 category criterion.8 However, based 7th and 8th edition AJCC staging systems demonstrated
on the impracticality of measuring tumor thickness to the that tumor mitotic rate, when explored across its dynamic
nearest 0.01 mm, especially for tumors [ 1 mm in tumor range, was a very important prognostic factor and strongly
thickness, in the 8th edition, the AJCC recommends that supports that if interrogated in this fashion, will likely be
tumor thickness be recorded to the nearest 0.1 mm and has an important covariate going forward as clinical tools are
provided a formal rounding schema to standardize the developed. As emphasized by the AJCC melanoma expert
approach.7 For example, patients with melanomas panel, for these reasons, mitotic rate should be collected for
0.75–0.84 mm in tumor thickness will now be rounded to all invasive melanomas.7,13
(and reported as) 0.8 mm (i.e., T1b), and melanomas Comparison of stages I and II substage melanoma-
between 0.95 mm and 1.04 mm in tumor thickness will be specific survival rates between the AJCC 7th and 8th edi-
reported as 1.0 mm (i.e., T1b). In the 8th edition, the tions demonstrate more favorable survival in the 8th
definitions of Tis, T0, and TX have been refined and/or edition compared with the 7th edition. An important con-
clarified. Tis is used for melanoma in situ (i.e., no invasive tributing factor was the requirement that to be included in
component is present). T0 is designated when no evidence the 8th edition analysis, SLN biopsy had to be performed
of a primary tumor can be found (e.g., a patient presenting for patients with T2 and thicker melanomas, and if per-
with an inguinal nodal metastasis of melanoma with no formed in patients with a T1 melanoma, the status of the
evidence of a primary tumor). TX is used when the tumor SLN was used.7,8,13,20 This approach ensured that patients
thickness cannot be determined (e.g., in a curettage spec- with clinically occult nodal metastases (detected by SLN
imen when there is no sectioning of the tumor biopsy) were designated as stage III in the 8th edition. In
perpendicular to the skin surface) or there is no information contrast, SLN biopsy was not required for inclusion in the
about the T category for the primary tumor (e.g., a primary 7th edition survival analyses for any tumor thickness (and
melanoma that was resected many years previously and the indeed many patients included in the dataset were managed
primary melanoma report cannot be found). before the era of SLN biopsy). As such, in the 7th edition
Based on previously published studies that reported database, many patients with clinically localized melanoma
patients with thicker T1 melanomas have a worse prog- who did not undergo SLN biopsy were characterized as
nosis than those with thinner T1 melanomas, the AJCC having stage I or II melanoma regardless of whether they
melanoma expert panel explored the potential impact of harbored clinically occult regional node metastasis,
including an additional tumor thickness criterion for sub- because only clinical staging of their nodal basin was
categorizing T1 melanomas by analyzing our IMDDP performed. A sequela of this 7th edition approach was that
melanoma database.10–13 With the proposal in place to the survival outcomes across multiple T subcategories were
record tumor thickness measurements to the nearest likely underestimated and, given the increasing relative
0.1 mm, a 0.8 mm cut point was explored for patients with risk of tumor-involvement of SLNs with increasing T
T1 melanoma along with ulceration and mitosis (i.e., \ 1 category, was most evident when comparing outcomes to
vs. C 1 mitosis/mm2). In this analysis, the addition of a those of the 8th edition for patients with T4b melanomas
0.8-mm tumor thickness stratum was a more powerful (Fig. 1a, b).
prognostic factor than mitotic rate (as a dichotomous
variable). Principally for this reason, mitotic rate as a N CATEGORY AND STAGE III STAGE GROUPS
dichotomous variable was removed as a T1 subcategory
criterion. The subcategorization of T1 melanomas at a 0.8- For the N category, which includes regional lymph node
mm threshold has potential clinical relevance, particularly as well as non-nodal regional disease (i.e., satellites, in-
for the role of SLN biopsy in patients with T1 melanomas. transit metastasis, and microsatellites), the AJCC mela-
Overall, SLN metastases are very infrequent (\ 5%) in noma expert panel grouped nonnodal regional disease
patients whose melanoma is \ 0.8 mm in thickness and together for staging purposes (because they each had a
nonulcerated (i.e., AJCC 8th edition T1a) but occur in similar impact on prognosis) and revised the N category
approximately 5–12% of patients with primary melanomas criteria.7 Previously used terms of ‘‘microscopic’’ and
0.8–1.0 mm in thickness (i.e., AJCC 8th edition T1b).14–17 ‘‘macroscopic’’ regional disease in the 7th edition have
Reflective of these data, consensus guidelines have rec- been replaced by ‘‘clinically occult’’ (i.e., detected by SLN
ommended that SLN biopsy may be considered in this biopsy) and ‘‘clinical evident’’ (i.e., detected by clinical
latter group of patients (i.e., patients with a primary tumor examination or radiographic imaging) regional disease to
thickness 0.8–1.0 mm) and also in patients with thinner enhance clarity. These correspond to N category designa-
ulcerated tumors (i.e., all patients with AJCC 8th edition tions ‘‘a’’ and ‘‘b’’, respectively. The presence of
T1b melanomas).18,19 Although mitosis was removed as a microsatellites, satellites, or in-transit metastases is now
T1 subcategory criterion, analyses performed for both the
Melanoma Staging: American Joint Committee on Cancer (AJCC) 8th Edition and Beyond 2107

a b

Melanoma-Specific Survival Probability

1.0 1.0
0.9 IA (n = 9,452)
0.9

Survival Rate (proportion)

0.8 IB (n = 8,918)
0.8
0.7 0.7
0.6 IIA (n = 4,644)
0.6
0.5 0.5
N 5-YR 10-YR IIB (n = 3,228)
0.4 0.4
IA 5225 99% 98%
IB 5749 97% 94% 0.3 IIC (n = 1,397)
0.3
IIA 2338 94% 88%
0.2 IIB 1688 87% 82% 0.2
IIC 691 82% 75% 0.1
0.1

0 1 2 3 4 5 6 7 8 9 10 0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0

Years Since Diagnosis Time (years)

c d
Melanoma-Specific Survival Probability

1.0 1.0
0.9 0.9

Survival Rate (proportion)

0.8 0.8
0.7 0.7 IIIA (n = 1,196)
0.6 0.6
0.5 0.5
0.4 0.4 IIIB (n = 1,391)

0.3 N 5-YR 10-YR 0.3

IIIA 1006 93% 88% IIIC (n = 720)
0.2 IIIB 1170 83% 77% 0.2
IIIC 2201 69% 60% 0.1
0.1
IIID 205 32% 24%

0 1 2 3 4 5 6 7 8 9 10 0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0

Years Since Diagnosis Time (years)

FIG. 1 Comparison of survival curves for 8th edition and 7th edition Joint Committee on Cancer eighth edition cancer staging manual. CA
AJCC stages I, II, and III. a 8th edition stages I and II stage groups; Cancer J Clin. 2017;67:472–92. Figures b and d used with
b 7th edition stages I and II stage groups; c 8th edition stage III stage permission from Balch CM, Gershenwald JE, Soong SJ, et al. Final
groups; and d 7th edition stages III stage groups. Figures a and c used version of 2009 AJCC melanoma staging and classification. J Clin
with permission from Gershenwald, J.E., Scolyer, R.A., Hess, K.R., Oncol. 2009;27:6199–206
et al. Melanoma staging: Evidence-based changes in the American

categorized as N1c, N2c, or N3c, based on the number of have had a CLND from those who have not, the ‘‘(sn)’’
tumor-involved regional lymph nodes, if any.7 Importantly, suffix should be appended to the N category for those who
the definition of a microsatellite was refined and clarified; a did not undergo CLND—i.e., a patient with a single tumor-
microsatellite is a microscopic cutaneous and/or subcuta- involved SLN who does not undergo CLND is
neous metastasis adjacent or deep to, but discontinuous pN1a(sn).7,8,13 This approach will likely improve data
from, a primary melanoma detected on pathological capture and facilitate future planned analyses in this new
examination of the primary tumor site. era of a more selective approach to CLND.
Recent clinical trial data, demonstrating no clear sur- Recognizing the importance of tumor thickness as a
vival benefit for patients with a tumor-involved SLN who potential prognostic factor among patients with regional
underwent completion lymph node dissection (CLND) disease and expanding on prior analyses demonstrating the
compared with those who did not, has already begun to importance of primary tumor ulceration among these
transform surgical approaches for patients with tumor-in- patients, the AJCC explored the prognostic impact of pri-
volved SLNs—i.e., fewer patients undergo completion mary tumor factors (e.g., tumor thickness and ulceration
lymph node dissection (CLND) after detection of a tumor- status), as well as regional factors via a T-category- and
involved SLN.21,22 It is worth noting that the 8th edition N-category-based analysis. Based on recursive partitioning
AJCC Cancer Staging Manual provides specific recom- analysis, the expert panel agreed on four stage III substages
mendations for documentation of the now common to capture the significant heterogeneity among the stage III
scenario when SLN biopsy identifies tumor-involved SLNs population.13 It is important to note that no direct com-
but CLND is not performed.9 To distinguish patients who parison or ‘‘mapping’’ of the 7th edition and 8th edition
2108 J. E. Gershenwald, R. A. Scolyer

pathological stage III stage groups is possible. First, tumor AJCC Eighth Edition
thickness was included as a component of stage III stage Melanoma Stage III Subgroups
groups for the 8th edition but was not employed as a stage
N T Category
III stage group criterion in the 7th edition melanoma
Category T0 T1a T1b T2a T2b T3a T3b T4a T4b
staging system. Furthermore, the N category criteria differ
in the 7th and 8th editions and, in several instances, the N1a N/A A A A B B C C C
various N subcategories map to different stage III group-
N1b B B B B B B C C C
ings in the 8th edition. With these important caveats in
mind, melanoma-specific survival (MSS) for both AJCC N1c B B B B B B C C C
8th edition stage IIIA and stage IIIB patients was more
favorable compared to 7th edition stage IIIA patients N2a N/A A A A B B C C C

(Fig. 1). These observations translate into significant N2b C B B B B B C C C

implications for patient counseling, management, and
contemporary clinical trial design, stratification, and anal- N2c C C C C C C C C C

ysis, because patients in the 8th edition cohort had a more N3a N/A C C C C C C C D
favorable survival profile across stages IIIA, IIIB, and IIIC
disease compared with patients with similar stage group- N3b C C C C C C C C D
ings in the 7th edition (Figs. 1c and d). To facilitate N3c C C C C C C C C D
accurate and efficient 8th edition stage III stage group
Instructions Legend
determination, particularly in busy patient clinics, clinic-, (1) Select patient’s N category at left chart.
(2) Select patient’s T category at top of chart. A Stage IIIA
desktop-, and phone-friendly stage III subgroup grids are
(3) Note letter at the intersection of T&N on grid.
available for download in the supporting information sec- (4) Determine patient’s AJCC stage using legend.
B Stage IIIB
tion of reference13 (reproduced in Fig. 2). C Stage IIIC
In recent years, multiple studies of patients with tumor-
N/A=Not assigned D Stage IIID
involved SLNs have demonstrated that SLN tumor burden
provides important prognostic information.23,24 SLN tumor
burden can be quantitated by a variety of parameters, such FIG. 2 American Joint Committee on Cancer (AJCC) eighth edition
stage III subgroups based on T and N categories. Used with
as the maximum size of the largest metastasis, the maxi- permission from Gershenwald JE, Scolyer RA, Hess KR, Sondak
mum subcapsular depth of extension of the tumor deposit VK, et al. Melanoma staging: evidence-based changes in the
(also known as the tumor penetrative depth), the location of American Joint Committee on Cancer eighth edition cancer staging
the deposit(s) within the SLN, and the percentage cross- manual. CA Cancer J Clin. 2017; 67:472–491
sectional area of the SLN involved by tumor.25,26 Micro-
scopic tumor burden has already been implemented as an the importance of central nervous system (CNS) disease in
inclusion criterion in some clinical trials of adjuvant ther- prognosis, clinical management, and clinical trial design,
apy.5 Based on available data and practical considerations, stratification, and analysis, a new M1d designation for
the AJCC melanoma expert panel recommends that the distant metastasis to the CNS has been added; M1c no
single largest maximum dimension (measured in millime- longer includes patients with CNS metastasis. In addition,
ters using an ocular micrometer) of the largest discrete M1c is no longer defined by any patient with distant
metastatic melanoma deposit in any tumor-involved SLN metastasis and elevated LDH. Nevertheless, as elevated
be recorded in pathology reports. Although this LDH has been demonstrated to be an adverse prognostic
histopathological parameter is not currently a formal factor both in the 7th edition analyses and recent clinical
staging criterion, SLN tumor burden will be included in trials, it remains an M category criterion in the 8th edi-
and will likely guide the development of future prognostic tion.2,3,7 The revised M category now includes a suffix to
models and ultimately validated clinical tools (e.g., calcu- signify the absence or presence of an elevated LDH for
lators, nomograms, etc.) for patients with regional each M1 subcategory.
metastatic disease.
BEYOND TNM, ASSESSMENT OF CLINICAL
M CATEGORY PROGNOSTIC TOOLS, AND NEXT STEPS

Patients with distant metastasis continue to be defined Additional prognostic factors that are not staging criteria
by anatomic site of distant metastases and serum lactate but are recommended for recording clinical care, emerging
dehydrogenase (LDH) level. In the 8th edition, reflective of prognostic factors for clinical care, as well as
Melanoma Staging: American Joint Committee on Cancer (AJCC) 8th Edition and Beyond 2109

recommendations for clinical trial stratification are also individualizing prognostic—and even predictive—assess-
presented in the 8th edition AJCC Cancer Staging Manual ment and enhance clinical decision making for patients
and/or on the AJCC website.7,27 with melanoma.29,31 Failure to maintain relevance in this
Despite its success over the past several decades, TNM/ exciting and unprecedented era of cancer discovery that is
anatomic-based staging systems have been constrained in translating into improved patient outcomes will eventually
their ability to accommodate prognostic factors that may render any staging system or prognostic model less rele-
emerge from an improved understanding of cancer biology. vant and potentially obsolete.
To be useful, any staging system needs to be clinically
relevant, reflect contemporary practice, and be refined as ACKNOWLEDGEMENT This work was supported in part by The
University of Texas MD Anderson Cancer Center Melanoma Moon
our understanding of the disease matures. In an effort to Shots Program; by the Robert and Lynne Grossman Family Foun-
foster clinical relevance, the AJCC has expanded its prin- dation; and by the Michael and Patricia Booker Melanoma Research
ciples of cancer staging to include nonanatomic-based Endowment. Support from the Australian National Health and Med-
factors. Nevertheless, it is essential that before such factors ical Research Council and colleagues at Melanoma Institute Australia
and Royal Prince Alfred Hospital is also gratefully acknowledged.
are introduced as staging criteria (and therefore adopted in
routine clinical settings), they are demonstrated to have
REFERENCES
independent prognostic significance, are validated in
independent patient cohorts, and are practical to measure in 1. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined
routine clinical practice. Using a systematic search of the Nivolumab and Ipilimumab or Monotherapy in Untreated Mela-
published literature, a priori criteria were used to evaluate noma. N Engl J Med. 2015;373:23–34.
quality and clinical relevance of 17 clinical prognostic 2. Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and
MEK inhibition versus BRAF inhibition alone in melanoma. N
tools for primary cutaneous melanoma; a principal con- Engl J Med. 2014;371:1877–88.
clusion was that there ‘‘is a great opportunity to improve 3. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus
these tools and to foster the development of new, validated ipilimumab in advanced melanoma. N Engl J Med.
tools by the inclusion of contemporary clinicopathological 2015;372:2521–32.
4. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall sur-
covariates and by using improved statistical and method- vival with combined nivolumab and ipilimumab in advanced
ological approaches.’’28 Formal criteria also have been melanoma. N Engl J Med. 2017;377:1345–56.
recently developed by the AJCC 8th edition Precision 5. Long GV, Hauschild A, Santinami M, et al. Adjuvant Dabrafenib
Medicine Core to serve as a framework for approval of plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J
Med. 2017;377:1813–23.
contemporary risk models by the AJCC.29 These changes 6. Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab
are overall reflective of a strategic evolution from popu- versus ipilimumab in resected stage III or IV melanoma. N Engl J
lation-based staging to a more personalized approach.29,30 Med. 2017;377:1824–35.
Given the ongoing advances in our understanding of the 7. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma of the
skin. In: Amin MB, et al. (eds) AJCC cancer staging manual.
clinical, pathological, molecular, and immunological Switzerland: Springer, 2017:563–85.
underpinnings of melanoma, a less ‘‘staccato’’ approach to 8. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of
cancer staging is likely to be embraced and implemented 2009 AJCC melanoma staging and classification. J Clin Oncol.
by the AJCC. Strategically configured iterative or ‘‘rolling’’ 2009;27:6199–206.
9. Gress DM, Edge SB, Greene FL, et al. Principles of cancer
updates can more efficiently exploit integration of clini- staging. In: Amin MB, et al. (eds) AJCC cancer staging manual.
cally relevant advances into the cancer staging arena. It is Switzerland: Springer, 2017:3–30.
important to note that while there is tremendous enthusi- 10. Gimotty PA, Elder DE, Fraker DL, et al. Identification of high-
asm to integrate molecular and/or immune-based risk patients among those diagnosed with thin cutaneous mela-
nomas. J Clin Oncol. 2007;25:1129–34.
biomarkers into melanoma staging and other clinical 11. Green AC, Baade P, Coory M, et al. Population-based 20-year
prognostic tools, there are as yet no formally validated survival among people diagnosed with thin melanomas in
schema. In addition, some biomarkers may have predictive Queensland, Australia. J Clin Oncol. 2012;30:1462–7.
significance but not prognostic significance. Overall, no 12. Lo SN, Scolyer RA, Thompson JF. Long-term survival of patients
with thin (T1) cutaneous melanomas: a Breslow thickness cut
molecular or immune biomarkers or signature currently point of 0.8 mm separates higher-risk and lower-risk tumors. Ann
fulfill the necessary criteria for inclusion into the AJCC Surg Oncol. 2018;25:894–902.
melanoma staging system or as a component of a validated 13. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging:
clinical tool. evidence-based changes in the American Joint Committee on
Cancer eighth edition cancer staging manual. CA Cancer J Clin.
Opportunities abound to leverage the expanding reper- 2017;67:472–92.
toire of electronic data collection efforts to facilitate 14. Andtbacka RH, Gershenwald JE. Role of sentinel lymph node
development, validation, implementation, and use of clin- biopsy in patients with thin melanoma. J Natl Compr Canc Netw.
ically relevant clinical calculators and tools to more 2009;7:308–17.
accurately stage patients. Such approaches will enable
2110 J. E. Gershenwald, R. A. Scolyer

15. Cordeiro E, Gervais MK, Shah PS, et al. Sentinel lymph node 24. van der Ploeg AP, van Akkooi AC, Haydu LE, et al. The prog-
biopsy in thin cutaneous melanoma: A systematic review and nostic significance of sentinel node tumour burden in melanoma
meta-analysis. Ann Surg Oncol. 2016;23:4178–88. patients: an international, multicenter study of 1539 sentinel
16. Han D, Zager JS, Shyr Y, et al. Clinicopathologic predictors of node-positive melanoma patients. Eur J Cancer.
sentinel lymph node metastasis in thin melanoma. J Clin Oncol. 2014;50:111–20.
2013;31:4387–93. 25. Scolyer RA, Li LX, McCarthy SW, et al. Micromorphometric
17. Murali R, Haydu LE, Quinn MJ, et al. Sentinel lymph node features of positive sentinel lymph nodes predict involvement of
biopsy in patients with thin primary cutaneous melanoma. Ann nonsentinel nodes in patients with melanoma. Am J Clin Pathol.
Surg. 2012;255:128–33. 2004;122:532–9.
18. Wong SL, Faries MB, Kennedy EB, et al. Sentinel lymph node 26. Murali R, Cochran AJ, Cook MG, et al. Interobserver repro-
biopsy and management of regional lymph nodes in melanoma: ducibility of histologic parameters of melanoma deposits in
American Society of Clinical Oncology and Society of Surgical sentinel lymph nodes: implications for management of patients
Oncology Clinical Practice Guideline Update. Ann Surg Oncol. with melanoma. Cancer. 2009;115:5026–37.
2018;25:356–77. 27. American Joint Committee on Cancer. https://cancerstaging.org/
19. Wong SL, Faries MB, Kennedy EB, et al. Sentinel lymph node references-tools/deskreferences/Pages/Supplementary-Material.a
biopsy and management of regional lymph nodes in melanoma: spx. Accessed 2 March 2018.
American Society of Clinical Oncology and Society of Surgical 28. Mahar AL, Compton C, Halabi S, et al. Critical assessment of
Oncology Clinical Practice Guideline Update. J Clin Oncol. clinical prognostic tools in melanoma. Ann Surg Oncol.
2018;36:399–413. 2016;23:2753–61.
20. Melanoma of the skin. In: Edge SB, et al. (eds) AJCC cancer 29. Kattan MW, Hess KR, Amin MB, et al. American Joint Com-
staging manual. Philadelphia: Springer, 2010:325–46. mittee on Cancer acceptance criteria for inclusion of risk models
21. Faries MB, Thompson JF, Cochran AJ, et al. Completion dis- for individualized prognosis in the practice of precision medicine.
section or observation for sentinel-node metastasis in melanoma. CA Cancer J Clin. 2016;66:370–4.
N Engl J Med. 2017;376:2211–22. 30. Amin MB, Edge SB, Greene FL, et al. Organization of the AJCC
22. Leiter U, Stadler R, Mauch C, et al. Complete lymph node dis- cancer staging manual. In: Amin MB, et al. AJCC cancer staging
section versus no dissection in patients with sentinel lymph node manual. Switzerland: Springer, 2017) 31–7.
biopsy positive melanoma (DeCOG-SLT): a multicentre, ran- 31. Compton CC, Hess, K.R., Halabi, S., et al. Risk models for
domised, phase 3 trial. Lancet Oncol. 2016;17:757–67. individualized prognosis in the practice of precision oncology. In:
23. Gershenwald JE, Andtbacka RH, Prieto VG, et al. Microscopic Amin MB, et al. (eds) AJCC cancer staging manual. Switzerland,
tumor burden in sentinel lymph nodes predicts synchronous Springer, 2017:47–52.
nonsentinel lymph node involvement in patients with melanoma.
J Clin Oncol. 2008;26:4296–303.